Е.И. Антонова1, Н.В. Фирсова2, Е.В. Балацюк3, Д.А. Викторов4, А.Б. Ачилов5

1–5 Научно-исследовательский центр фундаментальных и прикладных проблем биоэкологии и биотехнологии ФГБОУ ВО Ульяновский государственный педагогический университет им. И.Н. Ульянова (г. Ульяновск, Россия)

1 antonov_67@mail.ru, 2 n-firsova@mail.ru, 3 balacyxa@mail.ru, 4 viktorov.da@gmail.com, 5 a.achilow@inbox.ru

Постановка проблемы. Высокая скорость и чувствительность, мультиплексность, специфичность диагностики биологических образцов являются отличительными особенностями хМАР-технологии. Эта технология нашла применение как в области анализа образцов клинического материала, так и в области фундаментальных исследований. Анализируемыми объектами являются нуклеиновые кислоты, белки-антитела, ферменты, лиганды рецепторов, которые в лабораториях определяются традиционными методами диагностики («золотой диагностический стандарт»), такими как полимеразная цепная реакция (ПЦР), количественная ПЦР в реальном времени (qPCR), ПЦР с обратной транскрипцией (RT-PCR), количественная ПЦР с обратной транскрипцией (RT-qPCR), иммуноферментный анализ (ELISA). В то же время данные методы исследования имеют ограничения – неспособность одновременно обнаруживать несколько анализируемых веществ в одной реакции. Развитие хМАР-технологии (x – анализируемый материал, MAP – профилирование по нескольким анализируемым веществам) как метода диагностики во многом определено растущим объемом протеомных, транскриптомных и геномных данных большого числа организмов. Несмотря на то, что ПЦР позволяет проводить мультиплексную амплификацию нескольких мишеней за один запуск, xMAP, как методология, разработанная с целью создания высокопроизводительной платформы биоанализа, обеспечивает быстрый, экономичный и одновременный анализ нескольких веществ в одном биологическом образце и используется в фармацевтических, клинических и исследовательских лабораториях.

Цель работы – ретроспективный мета- и библиометрический анализ в формате «scoping review» (аналитический обзор) опубликованных экспериментальных и фундаментальных исследований в области применения хМАР-технологии для расширенного и углубленного ознакомления с возможностями технологии и более широкого в дальнейшем ее применения как современного и перспективного мультиплексного метода исследования в области практической медицины и в области фундаментальных исследований.

Результаты. В обзоре представлены систематизированные данные, которые отражают как общий принцип технологии, так и различные подходы, форматы технологии мультиплексного анализа, в зависимости от типа анализируемого вещества – формат анализа нуклеиновых кислот (MBMNA) и мультиплексного иммуноанализа (MBMI), и технологии с описанием подходов и сферой применения.

Практическая значимость. Данный обзор дает возможность получить развернутое и систематизированное представление по вопросу более широкого использования в исследовательской и клинической сфере перспективного мультиплексного метода исследования, поскольку одной из главных задач современного исследователя является поиск релевантной информации, обладающей научной ценностью.

Антонова Е.И., Фирсова Н.В., Балацюк Е.В., Викторов Д.А., Ачилов А.Б. хМАР-технологии в области диагностики заболеваний и фундаментальных исследований // Технологии живых систем. 2025. T. 22. № 1. С. 42-59. DOI: https://doi.org/10.18127/ j20700997-202501-04

1. Reslova N., Michna V., Kasny M. et al. xMAP Technology: Applications in Detection of Pathogens // Frontiers in Microbiology. 2017. V. 8. DOI: 10.3389/fmicb.2017.00055
2. Dunbar S.A. Nucleic acid sample preparation techniques for bead-based suspension arrays // Methods. 2023. V. 219. P. 22–29. DOI: 10.1016/j.ymeth.2023.09.003
3. Dunbar S.A. Applications of Luminex (R) xMAP (TM) technology for rapid, high-throughput multiplexed nucleic acid detection // Clinica Chimica Acta. 2006. V. 363. P. 71–82. DOI: 10.1016/j.cccn.2005.06.023
4. Taylor J. D., Briley, D., Nguyen, Q. et al. Flow cytometric platform for high-throughput single nucleotide polymorphism analysis // Biotechniques. 2001. V. 30. P. 661–666.
5. Wuyts V., Roosens, N.H.C., Bertrand S. et al. Guidelines for optimisation of a multiplex oligonucleotide ligation-PCR for characterisation of microbial pathogens in a microsphere suspension array // Biomed. Res. Int. 2015. V. 10. DOI: 10.1155/2015/790170
6. Iannone M.A., Taylor J.D., Chen J. et al. Multiplexed single nucleotide polymorphism genotyping by oligonucleotide ligation and flow cytometry // Cytometry. 2000. V. 39. P. 131–140. DOI: 10.1002/(SICI)1097-0320(20000201)39:2<131::AID-CYTO6>3.0.CO;2-U
7. Weis J.H., Tan S.S., Martin B.K., Wittwer C.T. Detection of rare mRNAs via quantitative RT-PCR // Trends Genet. 1992. V. 8. P. 263–264. DOI: 10.1016/0168-9525(92)90242-V
8. Engvall E., Perlmann P. Enzyme-linked immunosorbent assay (ELISA) Quantitative assay of immunoglobulin-G // Immunochemistry. 1971. V. 8. P. 871–874. DOI: 10.1016/0019-2791(71)90454-X
9. Angeloni S., Cordes R., Dunbar S. et al. xMAP Cookbook: A Collection of Methods and Protocols for Developing Multiplex Assays with xMAP Technology, 2nd Edn. (Austin, TX: Luminex). 2014.
10. Dunbar S., Li D. Introduction to Luminex® xMAP® technology and applications for biological analysis in China // Asia Pac. Biotech. 2010. V. 14. P. 26–30.
11. Angeloni S., et al. The xMAP® Cookbook, 5th Edition. P. 126-129, https://info.luminexcorp.com/en-us/research/download-the-xmapcookbook. 2022.
12. Qiagen. QIAamp® MinElute® Virus Spin Handbook. https://www.qiagen.com/us/resources/resourcedetail?id=8798cda6-4c55-4c0e-a302-966521c81aec&lang=en. 2020
13. Scerri J., Baldacchino S., Saliba C. et al. Bead-based RNA multiplex panels for biomarker detection in oncology samples // Methods. 2019. V. 158. P. 86–91.
14. LuminexCorporation, xTAG® CYP2C19 Kit v3 Package Insert (US). 2020.
15. LuminexCorporation. xTAG® Cystic Fibrosis 60 kit v2 Package Insert. 2022.
16. Qiagen. Storage of DNA. 2023 August 29, 2023]. Available from: https://www.qiagen.com/us/knowledge-and-support/knowledge-hub/bench-guide/dna/handling-dna/storage-of-dna
17. Tiwari A.K., Zai C.C., Altar C.A. et al. Clinical utility of combinatorial pharmacogenomic testing in depression: A Canadian patient- and rater-blinded, randomized, controlled trial // Translational Psychiatry. 2022. V. 12 (1). Article 101. DOI: 10.1038/s41398-022-01847-8
18. Loderstädt U., Hagen R.M., Hahn A., Frickmann H. New developments in PCR-based diagnostics for bacterial pathogens causing gastrointestinal infections-a narrative mini-review on challenges in the tropics // Trop. Med. Infectious Diseases. 2021. V. 6 (2). P. 96.
19. Houser B. Bio-Rad’sBio-Plex (R) suspension array system, xMAP technology overview // Arch. Physiol. Biochem. 2012. V. 118. P. 192–196. DOI: 10.3109/13813455.2012.705301
20. Tang Y., Stratton C. Advanced techniques in diagnostic microbiology. Berlin: Springer. 2006.
21. Nolan J.P., White P.S., Cai H. DNA Polymorphism Identity Determination Using Flow Cytometry.US 20020015962 A1. 2001.
22. Defoort J.P., Martin M., Casano B. et al. Simultaneous detection of multiplex-amplified human immunodeficiency virus type 1 RNA, hepatitis C virus RNA, and hepatitis B virus DNA using a flow cytometer microsphere-based hybridization assay // J. Clin. Microbiol. 2000. V. 38. P. 1066–1071.
23. Page B.T., Kurtzman C.P. Rapid identification of Candida species and other clinically important yeast species by flow cytometry // J. Clin. Microbiol. 2005. V. 43. P. 4507–4514. DOI: 10.1128/JCM.43.9.4507-4514.2005
24. Righter D.J., Rurangirwa F.R., Call D.R., McElwain T.F. Development of a bead-based multiplex PCR assay for the simultaneous detection of multiple Mycoplasma species // Vet. Microbiol. 2011. V. 153. P. 246–256. DOI: 10.1016/j.vetmic.2011.06.010
25. Liu Y., Xu, Z.-Q., Zhang, Q. et al. Simultaneous detection of seven enteric viruses associated with acute gastroenteritis by a multiplexed luminex-based assay // J. Clin. Microbiol. 2012. V. 50. P. 2384–2389. DOI: 10.1128/JCM.06790-11
26. Letant S. E., Ortiz J.I., Tammero L.F.B. et al. Multiplexed reverse transcriptase PCR assay for identification of viral respiratory pathogens at the point of care // J. Clin. Microbiol. 2007. V. 45. P. 3498–3505. DOI: 10.1128/JCM.01712-07
27. Zubach V., Smart G., Ratnam S., Severini A. Novel microsphere-based method for detection and typing of 46 mucosal human papillomavirus types // J. Clin. Microbiol. 2012. V. 50. P. 460–464. DOI: 10.1128/JCM.06090-11
28. Christopher-Hennings J., Araujo K.P.C., Souza C.J.H. et al. Opportunities for bead-based multiplex assays in veterinary diagnostic laboratories // J. Vet. Diagn. Invest. 2013. V. 25. P. 671–691. DOI: 10.1177/1040638713507256
29. Livshits M.A., Mirzabekov A.D. Theoretical analysis of the kinetics of DNA hybridization with gel-immobilized oligonucleotides // Biophys. J. 1996. V. 71. P. 2795–2801. DOI: 10.1016/S0006-3495(96)79473-0
30. Kellar K.L., Iannone M.A. Multiplexed microsphere-based flow cytometric assays // Exp. Hematol. 2002. V. 30. P. 1227–1237. DOI: 10.1016/S0301-472X(02)00922-0
31. Lin Y.-C., Sheng W.-H., Chang S.-C. et al. Application of a microsphere-based array for rapid identification of Acinetobacter spp. with distinct antimicrobial susceptibilities // J. Clin. Microbiol. 2008. V. 46. P. 612–617. DOI: 10.1128/JCM.01798-07
32. Chen J.W., Iannone M.A., Li M.S. et al. A microsphere-based assay for multiplexed single nucleotide polymorphism analysis using single base chain extension // Genome Res. 2000. V. 10. P. 549–557. DOI: 10.1101/gr.10.4.549
33. Ye F., Li M.S., Taylor J.D. et al. Fluorescent microsphere-based readout technology for multiplexed human single nucleotide polymorphism analysis and bacterial identification // Hum. Mutat. 2001. V. 17. P. 305–316. DOI: 10.1002/humu.28
34. Landegren U., Kaiser R., Sanders J., Hood, L. A ligase-mediated gene detection technique // Science. 1988. V. 241. P. 1077–1080. DOI: 10.1126/science.3413476
35. Reslova N., Huvarova V., Hrdy J. et al. A novel perspective on MOL-PCR optimization and MAGPIX analysis of in-house multiplex foodborne pathogens detection assay // Scientific Reports. 2019. V. 9. P. 2719.
36. Nolan J., White P. Nucleic Acid Sequence Detection Using Multiplexed Oligonucleotide PCR.US 7153656 B2. 2004.
37. Deshpande A., Gans J., Graves S.W. et al. A rapid multiplex assay for nucleic acid-based diagnostics // J. Microbiol. Methods. 2010. V. 80. P. 155–163. DOI: 10.1016/j.mimet.2009.12.001
38. Thierry S., Hamidjaja R.A., Girault G. et al. A multiplex bead-based suspension array assay for interrogation of phylogenetically informative single nucleotide polymorphisms for Bacillus anthracis // J. Microbiol. Methods. 2013. V. 95. P. 357–365. DOI: 10.1016/j.mimet.2013.10.004
39. Bokken G.C., Bergwerff A.A., van Knapen F. A novel bead-based assay to detect specific antibody responses against Toxoplasma gondii and Trichinella spiralis simultaneously in sera of experimentally infected swine // BMC Vet. Res. 2012. V. 8. P. 36. DOI: 10.1186/1746-6148-8-36
40. Baker H.N., Murphy R., Lopez E., Garcia C. Conversion of a capture ELISA to a luminex xMAP assay using a multiplex antibody screening method // J. Vis. Exp. 2012. V. 6. P. 4084. DOI: 10.3791/4084
41. Nockler K., Voigt W.P., Protz D. et al. Indirect ELISA for the diagnosis of trichinosis in living pigs. Berl. Munch. Tierarztl. Wochenschr. 1995. V. 108. P. 167–174.
42. van der Wal F.J., Achterberg R.P., Kant A., Maassen C.B.M. A bead-based suspension array for the serological detection of Trichinella in pigs // Vet. J. 2013. V. 196. P. 439–444. DOI: 10.1016/j.tvjl.2012.10.029
43. Berry M., Gamieldien J., Fielding B.C. Identification of new respiratory viruses in the new millennium // Viruses Basel. 2015. V. 7. P. 996–1019. DOI: 10.3390/v7030996
44. Lei C., Lou C.T., Io K. et al. Viral etiology among children hospitalized for acute respiratory tract infections and its association with meteorological factors and air pollutants: a time-series study (2014–2017) in Macao // BMC Infectious Diseases. 2022. V. 22(1). Article 588. DOI: 10.1186/s12879-022-07585-y
45. Shi Y. et al. The Complex Co-infections of Multiple Porcine Diarrhea Viruses in Local Area Based on the Luminex xTAG Multiplex Detection Method // Front. Vet. Sci. 2021. V. 8. Article 602866.
46. Carter J.M. et al. Rapid, Multiplexed Characterization of Shiga Toxin-Producing Escherichia coli (STEC) Isolates Using Suspension Array Technology // Frontiers in Microbiology. 2016. V. 7. P. 439.
47. Neumann G., Chen H., Gao G.F. et al. H5N1 influenza viruses: outbreaks and biological properties // Cell Res. 2010. V. 20. P. 51–61. DOI: 10.1038/cr.2009.124
48. Zou S.M., Han H., Wen L.Y. et al. Human influenza A virus (H5N1) detection by a novel multiplex PCR typing method // J. Clin. Microbiol. 2007. V. 45. P. 1889–1892. DOI: 10.1128/JCM.02392-06
49. Washington C., Metzgar D., Hazbon M.H. et al. Multiplexed luminex xMAP assay for detection and identification of five adenovirus serotypes associated with epidemics of respiratory disease in adults // J. Clin. Microbiol. 2010. V. 48. P. 2217–2222. DOI: 10.1128/JCM.00029-10
50. Krunic N., Merante F., Yaghoubian S. et al. Advances in the diagnosis of respiratory tract infections: role of the luminex xTAG respiratory viral panel // Ann. N. Y. Acad. Sci. 2011. V. 1222. P. 6–13.
51. Selvaraju S.B., Selvarangan R. Evaluation of xTAG respiratory viral panel FAST and xTAG human parainfluenza virus analyte-specific reagents for detection of human parainfluenza viruses in respiratory specimens // Diagn. Microbiol. Infect. Dis. 2012. V. 72. P. 278–281. DOI: 10.1016/j.diagmicrobio.2011.11.005
52. Smith J., Sammons D., Toennis C. et al. Semi-quantitative analysis of influenza samples using the luminex xTAG (R) respiratory viral panel kit // Toxicol. Mech. Methods. 2012. V. 22. P. 211–217. DOI: 10.3109/15376516.2011.610387
53. Pabbaraju K., Wong S., Tokaryk K.L. et al. Comparison of the luminex xTAG respiratory viral panel with xTAG respiratory viral panel fast for diagnosis of respiratory virus infections // J. Clin. Microbiol. 2011. V. 49. P. 1738–1744. DOI: 10.1128/JCM.02090-10
54. Hamza I.A., Jurzik L., Wilhelm M. Development of a luminex assay for the simultaneous detection of human enteric viruses in sewage and river water // J. Virol. Methods. 2014. V. 204. P. 65–72. DOI: 10.1016/j.jviromet.2014.04.002
55. Beckmann C., Heininger U., Marti H., Hirsch H.H. Gastrointestinal pathogens detected by multiplex nucleic acid amplification testing in stools of pediatric patients and patients returning from the tropics // Infection. 2014. V. 42. P. 961–970. DOI: 10.1007/s15010-014-0656-7
56. Perry M.D., Garden S.A., Howe R.A. Evaluation of the luminex xTAG gastrointestinal pathogen panel and the savyon diagnostics gastrointestinal infection panel for the detection of enteric pathogens in clinical samples // J. Med. Microbiol. 2014. V. 63. P. 1419–1426. DOI: 10.1099/jmm.0.074773-0
57. Wessels E., Rusman L.G., van Bussel M.J., Claas E.C.J. Added value of multiplex luminex gastrointestinal pathogen panel (xTAG((R)) GPP) testing in the diagnosis of infectious gastroenteritis // Clin. Microbiol. Infect. 2014. V. 20. O182–O187. DOI: 10.1111/1469-0691.12364
58. Zboromyrska Y., Hurtado J.C., Salvador P. et al. Aetiology of traveller’s diarrhoea: evaluation of a multiplex PCR tool to detect different enteropathogens // Clin. Microbiol. Infect. 2014. V. 20. P. O753–O759. DOI: 10.1111/1469-0691.12621
59. Deng J.K., Luo X., Wang R.L. et al. A comparison of luminex xTAG (R) Gastrointestinal Pathogen Panel (xTAG GPP) and routine tests for the detection of enteropathogens circulating in Southern China // Diagn. Microbiol. Infect. Dis. 2015. V. 83. P. 325–330. DOI: 10.1016/j.diagmicrobio.2015.07.024
60. Jiang H.-L., Zhu H.-H., Zhou L.-F. et al. Genotyping of human papillomavirus in cervical lesions by L1 consensus PCR and the Luminex xMAP system // J. Med. Microbiol. 2006. V. 55. P. 715–720. DOI: 10.1099/jmm.0.46493-0
61. Lowe B., Kobayashi L., Lorincz A. et al. HPV genotype detection using hybrid capture sample preparation combined with whole genome amplification and multiplex detection with luminex XMAP // J. Mol. Diagn. 2010. V. 12. P. 847–853. DOI: 10.2353/jmoldx.2010.100045
62. Clayton B.A., Wang L.F., Marsh G.A. Henipaviruses: an updated review focusing on the pteropid reservoir and features of transmission // Zoonoses Public Health. 2013. V. 60. P. 69–83. DOI: 10.1111/j.1863-2378.2012.01501.x
63. Takada A., Kawaoka Y. The pathogenesis of Ebola hemorrhagic fever // Trends Microbiol. 2001. V. 9. P. 506–511. DOI: 10.1016/S0966-842X(01)02201-6
64. Bowden T.R., Bingham J., Harper J.A., Boyle D.B. Menangle virus, a pteropid bat paramyxovirus infectious for pigs and humans, exhibits tropism for secondary lymphoid organs and intestinal epithelium in weaned pigs // J. Gen. Virol. 2012. V. 93. P. 1007–1016. DOI: 10.1099/vir.0.038448-0
65. Boyd V., Smith I., Crameri G., Burroughs A.L. et al. Development of multiplexed bead arrays for the simultaneous detection of nucleic acid from multiple viruses in bat samples // J. Virol. Methods. 2015. V. 223. P. 5–12. DOI: 10.1016/j.jviromet.2015.07.004
66. Pearson P., Skaltsis O., Luo C-Y. et al. Borrelia burgdorferi outer surface protein C (OspC) genotyping method using Luminex technology // PLOS. 2022. V. 1. https://doi.org/10.1371/journal.pone.0269266)
67. Opalka D., Lachman C.E., MacMullen S.A. et al. Simultaneous quantitation of antibodies to neutralizing epitopes on virus-like particles for human papillomavirus types 6, 11, 16, and 18 by a multiplexed luminex assay 2 // Clin. Diagn. Lab. Immunol. 2003. V. 10. P. 108–115.
68. Diaz M.R., Fell J.W. High-throughput detection of pathogenic yeasts of the genus Trichosporon // J. Clin. Microbiol. 2004. V. 42. P. 3696–3706. DOI: 10.1128/JCM.42.8.3696-3706.2004
69. Kong W., Li Y., Cheng S. et al. Luminex xMAP combined with Western blot improves HIV diagnostic sensitivity // J. Virol. Methods 2016. V. 227. P. 1–5. DOI: 10.1016/j.jviromet.2015.10.007
70. Fonseca B.P.F., Marques C.F.S., Nascimento L.D. et al. Development of a multiplex bead-based assay for detection of Hepatitis C Virus // Clin. Vaccine Immunol. 2011. V. 18. P. 802–806. DOI: 10.1128/CVI.00265-10
71. duPont N.C., Wang K.H., Wadhwa P.D. et al. Validation and comparison of luminex multiplex cytokine analysis kits with ELISA: determinations of a panel of nine cytokines in clinical sample culture supernatants // J. Reprod. Immunol. 2005. V. 66. P. 175–191. DOI: 10.1016/j.jri.2005.03.005
72. Seck M.C., Badiane A.S., Thwing J. et al. Serological Data Shows Low Levels of Chikungunya Exposure in Senegalese Nomadic Pastoralists // Pathogens. 2019. V. 8(3). Article 113. https://doi.org/10.3390/pathogens8030113
73. Набор реагентов для выявления кДНК вируса гриппа типа А субтипов Н1, ИЗ, Н5, Н7 и Н9 на олигонуклеотидных суспензионных биочипах «Вектор-xMAP-Influenza Н1/НЗ/Н5/Н7/Н9, по ТУ 21.20.23-081-05664012-2017 на базе (ФБУН ГНЦ ВБ «Вектор» Роспотребнадзора)
74. Browne D.J., Liang F., Gartlan K.H. et al. Multiplex Microsphere PCR (mmPCR) Allows Simultaneous Gram Typing, Detection of Fungal DNA, and Antibiotic Resistance Genes // Laboratory Medicine. 2022. V. 53. Iss. 5. P. 459–464. https://doi.org/10.1093/labmed/lmac023
75. McQuiston J.R., Waters R.J., Dinsmore B.A. et al. Molecular determination of H antigens of Salmonella by Use of a microsphere-based liquid array // J. Clin. Microbiol. 2011. V. 49. P. 565–573. DOI: 10.1128/JCM.01323-10
76. Bio-Rad. InstaGene™ Matrix., 2023 August 29, 2023. Available from: https://www.bio-rad.com/en-us/product/instagene-matrix?ID=6c2be54f-6c95-43de-8ce3-e9aee8229eeb
77. Fitzgerald C., Collins M., van Duyne S. et al. Multiplex, bead-based suspension array for molecular determination of common Salmonella serogroups // J. Clin. Microbiol. 2007. V. 45. P. 3323–3334. DOI: 10.1128/JCM.00025-07
78. Onori M., Coltella L., Mancinelli L. et al. Evaluation of a multiplex PCR assay for simultaneous detection of bacterial and viral enteropathogens in stool samples of paediatric patients // Diagn. Microbiol. Infect. Dis. 2017. V. 79. P. 149–154. DOI: 10.1016/j.diagmicrobio.2014.02.004
79. Wilson W.J., Erler A.M., Nasarabadi S.L. et al. A multiplexed PCR-coupled liquid bead array for the simultaneous detection of four biothreat agents // Mol. Cell. Probes 2005. V. 19. P. 137–144. DOI: 10.1016/j.mcp.2004.10.005
80. Song J., Li P.-E., Gans J. et al. Simultaneous pathogen detection and antibiotic resistance characterization using SNP-based multiplexed oligonucleotide ligation-PCR (MOL-PCR) // Adv. Comput. Biol. 2010. V. 680. P. 455–464. DOI: 10.1007/978-1-4419-5913-3_51
81. Stucki D., Malla B., Hostettler S. et al. Two new rapid SNP-typing methods for classifying Mycobacterium tuberculosis complex into the main phylogenetic lineages // PLoS ONE 2012. V. 7. Article e41253. DOI: 10.1371/journal.pone.0041253
82. Dunbar S.A., Vander Zee C.A., Oliver K.G. et al. Quantitative, multiplexed detection of bacterial pathogens: DNA and protein applications of the Luminex LabMAP (TM) system // J. Microbiol. Methods. 2003. V. 53. P. 245–252. DOI: 10.1016/S0167-7012(03)00028-9
83. Jun B.H., Kang H., Lee Y.S., Jeong D.H. Fluorescence-based multiplex protein detection using optically encoded microbeads // Molecules 2012. V. 17. P. 2474–2490. DOI: 10.3390/molecules17032474
84. Kim J.S., Taitt C.R., Ligler F.S., Anderson G.P. Multiplexed magnetic microsphere immunoassays for detection of pathogens in foods // Sens. Instrum. Food Qual. Saf. 2010. V. 4. P. 73–81. DOI: 10.1007/s11694-010-9097-x
85. Silbereisen A., Tamborrini M., Wittwer M. et al. Development of a bead-based luminex assay using lipopolysaccharide specific monoclonal antibodies to detect biological threats from Brucella species // BMC Microbiol. 2015. V. 15. Article 198. DOI: 10.1186/s12866-015-0534-1
86. Simonova M.A., Petrova E.E., Dmitrenko O.A. et al. xMAP-based analysis of three most prevalent staphylococcal toxins in Staphylococcus aureus cultures // Anal. Bioanal. Chem. 2014. V. 406. P. 6447–6452. DOI: 10.1007/s00216-014-8048-5
87. Sheppard C.L., Harrison T.G., Smith M.D., George R.C. Development of a sensitive, multiplexed immunoassay using xMAP beads for detection of serotype-specific streptococcus pneumoniae antigen in urine samples // J. Med. Microbiol. 2011. V. 60. P. 49–55. DOI: 10.1099/jmm.0.023150-0
88. Sturm A., Vos M.W., Henderson R. et al. Barcoded Asaia bacteria enable mosquito in vivo screens and identify novel systemic insecticides and inhibitors of malaria transmission // PLOS Biology. 2021. DOI: 10.1371/journal.pbio.3001426
89. Navidad J.F., Griswold D.J., Gradus M.S., Bhattacharyya S. Evaluation of luminex xTAG gastrointestinal pathogen analyte-specific reagents for high-throughput, simultaneous detection of bacteria, viruses, and parasites of clinical and public health importance // J. Clin. Microbiol. 2013. V. 51. P. 3018–3024. DOI: 10.1128/JCM.00896-13
90. Taniuchi M., Verweij J.J., Noor Z. et al. High throughput multiplex PCR and probe-based detection with luminex beads for seven intestinal parasites // Am. J. Trop. Med. Hyg. 2011. V. 84. P. 332–337. DOI: 10.4269/ajtmh.2011.10-0461
91. Vernacchio L., Vezina R.M., Mitchell A.A. et al. Diarrhea in American infants and young children in the community setting // Pediatr. Infect. Dis. J. 2006. V. 25. P. 2–7. DOI: 10.1097/01.inf.0000195623.57945.87
92. Claudel L., Valeix N., Basmaciyan L. et al. Comparative Study of Eleven Mechanical Pretreatment Protocols for Cryptosporidium parvum DNA Extraction from Stool Samples // Microorganisms. 2021. V. 9 (2). P. 297.
93. Jansen A., Stark K., Kunkel J. et al. Aetiology of community-acquired, acute gastroenteritis in hospitalised adults: a prospective cohort study // BMC Infect. Dis. 2008. V. 8. P. 143. DOI: 10.1186/1471-2334-8-143
94. Friesema I.H.M., de Boer R.F., Duizer E. et al. Aetiology of acute gastroenteritis in adults requiring hospitalization in The Netherlands // Epidemiol. Infect. 2012. V. 140. P. 1780–1786. DOI: 10.1017/S0950268811002652
95. Claas E.C., Burnham C.-A.D., Mazzulli T. et al. Performance of the xTAG (R) gastrointestinal pathogen panel, a multiplex molecular assay for simultaneous detection of bacterial, viral, and parasitic causes of infectious gastroenteritis // J. Microbiol. Biotechnol. 2013. V. 23. P. 1041–1045. DOI: 10.4014/jmb.1212.12042
96. Mengelle C., Mansuy J.M., Prere M.F. et al. Simultaneous detection of gastrointestinal pathogens with a multiplex luminex-based molecular assay in stool samples from diarrhoeic patients // Clin. Microbiol. Infect. 2013. V. 19. P. E458–E465. DOI: 10.1111/1469-0691.12255
97. Nockler K., Pozio E., Voigt W.P., Heidrich J. Detection of Trichinella infection in food animals // Vet. Parasitol. 2000. V. 93. P. 335–350. DOI: 10.1016/S0304-4017(00)00350-2
98. Anderson J.P., Rascoe L.N., Levert K. et al. Development of a luminex bead based assay for diagnosis of toxocariasis using recombinant antigens Tc-CTL-1 and Tc-TES-26 // PLoS Negl. Trop. Dis. 2015. V. 9. P. e0004168. DOI: 10.1371/journal.pntd.0004168
99. Babady N.E., Miranda E., Gilhuley K.A. Evaluation of Luminex xTAG fungal analyte-specific reagents for rapid identification of clinically relevant fungi // J. Clin. Microbiol. 2011. V. 49. P. 3777–3782. DOI: 10.1128/JCM.01135-11
100. Galliano I., Daprà V., Zaniol E. et al. Comparison of methods for isolating fungal DNA // Pract. Lab. Med. 2021. V. 25. P. e00221.
101. Das S., Brown T.M., Kellar K.L. et al. DNA probes for the rapid identification of medically important Candida species using a multianalyte profiling system // FEMS Immunol. Med. Microbiol. 2006. V. 46. P. 244–250. DOI: 10.1111/j.1574-6968.2006.00424.x
102. Balada-Llasat J.M., LaRue H., Kamboj K. et al. Detection of yeasts in blood cultures by the luminex xTAG fungal assay // J. Clin. Microbiol. 2012. V. 50. P. 492–494. DOI: 10.1128/JCM.06375-11
103. Farooqi J., Jabeen K., Saeed N. et al. Species identification of invasive yeasts including Candida in Pakistan: limitations of phenotypic methods // J. Pak. Med. Assoc. 2012. V. 62. P. 995–998.
104. Landlinger C., Preuner S., Willinger B. et al. Species-specific identification of a wide range of clinically relevant fungal pathogens by use of luminex xMAP technology // J. Clin. Microbiol. 2009. V. 47. P. 1063–1073. DOI: 10.1128/JCM.01558-08
105. O’Donnell K., Sarver B.A.J., Brandt M. et al. Phylogenetic diversity and microsphere array-based genotyping of human pathogenic fusaria, including isolates from the multistate contact lens–Associated US Keratitis outbreaks of 2005 and 2006 // J. Clin. Microbiol. 2007. V. 45. P. 2235–2248. DOI: 10.1128/JCM.00533-07
106. Bovers M., Diaz M.R., Hagen F. et al. Identification of genotypically diverse Cryptococcus neoformans and Cryptococcus gattii isolates by luminex xMAP technology // J. Clin. Microbiol. 2007. V. 45. P. 1874–1883. DOI: 10.1128/JCM.00223-07
107. Massarenti L., Enevold C., Damgaard D. et al. Peptidylarginine Deiminase 2 Gene Polymorphisms in Subjects with Periodontitis Predispose to Rheumatoid Arthritis // Int. J. Mol. Sci. 2022. V. 23(17). P. 9536. DOI: 10.3390/ijms23179536
108. Massarenti L., Enevold C., Damgaard D. et al. PADI4 Polymorphisms Confer Risk of Anti-CCP-Positive Rheumatoid Arthritis in Synergy With HLA-DRB1*04 and Smoking // Front. Immunol. 2021. V. 12. DOI: 10.3389/fimmu.2021.707690
109. Ebbesen M., Enevold C., Juul A. et al. Insulin-Like Growth Factor Gene Polymorphisms Predict Clinical Course in Allogeneic Hematopoietic Stem Cell Transplantation // Front. Immunol. 2020. Sec. Alloimmunity and Transplantation. V. 11. DOI: 10.3389/fimmu.2020.01646
110. Zheng Y.-Y., Fei Y., Wang Z. et al. Tissue microRNAs in non-small cell lung cancer detected with a new kind of liquid bead array detection system // Journal of Translational Medicine. 2020. V. 18. P. 108.
111. Hansen E.O., Dias N.S., Burgos I.C.B. et al. Millipore xMap® Luminex (HATMAG-68K): An Accurate and Cost-Effective Method for Evaluating Alzheimer’s Biomarkers in Cerebrospinal Fluid // Frontiers in Psychiatry. 2021. V. 12. DOI: 10.3389/fpsyt.2021.716686
112. Paradis F.W., Simard R., Gaudet D. Quantitative assay for the detection of the V617F variant in the Janus kinase 2 (JAK2) gene using the Luminex xMAP technology // BMC Medical Genetics. 2010. V. 11. P. 54.
113. Taniguchi H., Okamoto W., Muro K. et al. Clinical Validation of Newly Developed Multiplex Kit Using Luminex xMAP Technology for Detecting Simultaneous RAS and BRAF Mutations in Colorectal Cancer: Results of the RASKET-B Study // Neoplasia. 2018. V. 20(12). P. 1219–1226. DOI: 10.1016/j.neo.2018.10.004
114. Клейменов Д.А., Мазунина Е.П., Лунин В.Г. и др. Иммунологическая память, формируемая в ответ на вакцинацию противотуберкулезной рекомбинантной вакциной «ГамТБвак»: клинические исследования вакцины на здоровых добровольцах // Вестник РГМУ. 2017. Т. 5. С. 29–37.